SYSTEM AND METHOD FOR IMPROVING DIAGNOSIS, PROGNOSIS AND / OR CLINICAL MANAGEMENT OF ANEMIA AND / OR BONE METABOLISM DISORDERS IN CHRONIC KIDNEY DISEASE

Description

1 / 27 Descriptive Report of Invention Patent System and Method for Improving Diagnosis, Prognosis, and / or Clinical Management of Anemia and / or Bone Metabolism Disorders in Chronic Kidney Disease Field of Invention

[0001] The present invention is situated in the field of medicine. More specifically, the invention provides a system for improving the quality of useful data in Nephrology. The invention is particularly useful for providing improved diagnostic, prognostic and / or clinical management parameters, providing rapid and safe improvements in the control of anemia and BMD in CKD. The invention is also useful for improving the performance of outpatient chronic hemodialysis units, hospital hemodialysis units, especially large-scale ones. Background of the Invention

[0002] Nephrology is the medical specialty dedicated to the diagnosis and clinical treatment of diseases of the urinary system, mainly related to the kidney. According to Medical Demographics in Brazil 2023, Brazil has almost 5,500 nephrologists.

[0003] Chronic Kidney Disease (CKD) consists of kidney damage and progressive and irreversible loss of kidney function, and in its most advanced stage (stage 5 or CKD-5), the kidneys can no longer maintain the normality of the body's internal environment, so that to maintain life, it is necessary to resort to Renal Replacement Therapy (RRT) treatment, such as hemodialysis or peritoneal dialysis, or even a kidney transplant.

[0004] In Brazil, CKD is a problem of great magnitude, with a progressive increase in the number of people affected over the last few years, reaching more than 150,000 people undergoing dialysis therapy in the country, in approximately 870 dialysis centers, according to the Census of the Brazilian Society of Petition 870250005827, dated 01 / 24 / 2025, page 5 / 36 2 / 27 Nephrology (SBN) 2022.

[0005] CKD-5 is accompanied by several complications in the patient's body, such as the accumulation of impurities (e.g., urea, potassium, and phosphorus), fluid retention, anemia, and bone mineral disorder. The present invention, also known as NAI, provides a system and method for integrating this data and improving diagnostic, prognostic, and / or clinical management parameters, and for improving the performance of outpatient chronic hemodialysis and hospital hemodialysis units, especially large-scale ones.

[0006] Anemia is a very common complication in patients with CKD, and its control is fundamental, since persistent anemia, in addition to worsening quality of life, significantly increases mortality. It is a multifactorial disease that manifests with varying intensities, requiring a specific therapeutic approach for each patient and for each stage of their life on dialysis. The main known cause is the reduced production of the hormone erythropoietin by the diseased kidneys. This hormone acts on the bone marrow, stimulating the production of red blood cells (erythrocytes), and its lack leads to a reduction in the production of blood cells and consequently to anemia.

[0007] Another important factor in the genesis of anemia is iron deficiency, resulting from reduced iron absorption in the intestine caused by CKD and increased blood loss in dialysis treatments. In addition to these, there are several other factors involved in the genesis of anemia in CKD, such as chronic inflammation and vitamin deficiency.

[0008] Given the complexity of the genesis of anemia in patients with CKD, its treatment is also complex, as it involves a multidisciplinary approach, requiring the monthly collection and analysis of various tests to determine which medications and at what dose will be used to control the condition, as well as behavioral, nutritional, and dialysis treatment process adjustments. Petition 870250005827, dated 01 / 24 / 2025, page 6 / 36 3 / 27

[0009] Among the routinely performed blood tests, the following stand out: hemoglobin or complete blood count, serum iron, transferrin saturation index, ferritin, and B complex vitamins (B9-folic acid and B12).

[0010] Among the main medications used in the treatment of this condition are alphaepoetin, iron hydroxide, vitamin B12, and folic acid. After starting their use, all of them should be monitored monthly, as excessive dosage can lead the patient to the opposite state of anemia, polycythemia, which can cause serious complications.

[0011] Disorders of bone mineral metabolism (BMD) in CKD lead to bone and cardiovascular diseases. In addition to potentially resulting in fractures, pain, bone deformities, and reduced growth velocity in children, BMD is also a risk factor for vascular calcification and is associated with cardiomyopathy and left ventricular hypertrophy, with a consequent increased risk of ischemic heart disease, heart failure, and death from cardiovascular causes. The common mechanisms between bone and cardiovascular disease are supported by growing evidence that alterations in bone remodeling favor the development of extraosseous calcifications, mainly vascular ones.

[0012] Bone mineral deficiency (BMD) is a syndrome with a wide spectrum of clinical, pathological, and laboratory manifestations, resulting from loss of kidney function, reduced excretion of phosphorus and calcium, decreased active vitamin D (calcitriol), alterations in parathyroid hormone (PTH), and fibroblast growth factor 23 (FGF-23). ​​Like anemia, BMD also has a complex genesis that is difficult to manage, requiring the performance and analysis of various tests and the administration of specific medications, in addition to behavioral and nutritional modifications and dialysis therapy. Routine blood tests include calcium (Ca), phosphorus (P), parathyroid hormone (PTH), vitamin D, and alkaline phosphatase. Medications used in the management of BMD include calcium-based phosphate binders (the main one being calcium carbonate), non-calcium-based phosphate binders (sevelamer), cinacalcet, Petition 870250005827, dated 01 / 24 / 2025, page 7 / 36 4 / 27 paricalcitol and calcitriol.

[0013] Technical difficulties associated with the guidance of Anemia and BMD Treatment and Dispensing of Medications.

[0014] The analysis of the tests and the definition of which medications to use and the titration of individualized doses for each patient must be done by the nephrologist every month for all of their patients, in light of the most current guidelines and regulations.

[0015] To assist in the management of these complex pathologies, nephrology societies around the world, especially the American and European Societies of Nephrology, write and periodically update guidelines for anemia (https: / / kdiqo.org / wp-content / uploads / 2016 / 10 / KDIGO-2012- Anemia-Guideline-Enqlish.pdf, KDOQI US Commentary on the 2012 KDIGO Clinical Practice Guideline for Anemia in CKD Kliger, Alan S. et al. American Journal of Kidney Diseases, Volume 62, Issue 5, 849 - 859) and DMO (https: / / kdiqo.org / wp-content / uploads / 2017 / 02 / 2017-KDIGO-CKD-MBD-GLUpdate.pdf)·

[0016] Because medications are essential to the lives of patients with CKD, in Brazil they are provided free of charge by the government through the Unified Health System (SUS). Due to the high cost of these medications, which need to be used continuously throughout the patient's life, the Ministry of Health has very strict regulations regarding the guidance on their use and dispensing, requiring the periodic submission of updated test results and the completion of specific requisitions. All these regulations are based on international recommendations and are frequently updated.

[0017] This set of factors and complexities requires that, every month, the nephrologist must evaluate all the tests of all their patients, and for each patient, perform an individualized analysis of the management of anemia and bone mineral density (BMD), defining which therapeutic strategies to adopt, which medications, and at what doses to use. This analysis is very complex and must involve knowledge of Petition 870250005827, dated 01 / 24 / 2025, page 8 / 36 5 / 27 current guidelines and regulations, the clinical situation and current tests of each patient. It should also consider the history of tests, medications in use, responses to each situation in previous months, patient adherence to treatments and allergies / intolerances, among other factors.

[0018] In addition to the great complexity of the aforementioned monthly analysis that the nephrologist must perform, there is also substantial time pressure, that is, the deadline for completing these tasks is very short. Firstly, because the faster the nephrologist can perform this analysis, the faster the patient will receive the necessary therapeutic adjustment for the correct treatment of their pathologies. Secondly, to obtain the release of medications from the Health Department, all duly completed and signed forms, prescriptions, and copies of the tests must be submitted before the end of the month, that is, a few days after the doctor has received the results of the test collected that month. The need for all this extensive evaluation leads to a series of problems that the inventor identified in several years of clinical practice. Among these are cited here:

[0019] Nephrologist's update - Dependence on how well the nephrologist knows and keeps up-to-date with guidelines and regulations, with the risk of defining procedures that are inconsistent with the most current guidelines and regulations. This situation also increases the risk of errors that can harm patients and eventually imply civil liability for the doctor and the clinic where he / she works.

[0020] Standardization of procedures - Even when nephrologists frequently update their knowledge, the interpretation of a specific clinical case in light of current guidelines and regulations, and the analysis of individual patient tests and medications, can vary greatly from doctor to doctor. This risks a lack of standardization of procedures among doctors in the same clinic, and even among different clinics within the same economic group, leading to difficulties in understanding on the part of the nursing staff, patients, and their families. Petition 870250005827, dated 01 / 24 / 2025, page 9 / 36 6 / 27

[0021] Manual Interpretation and Risk of Human Error - As mentioned above, the analysis that the nephrologist must perform is always extensive, complex, and recurring (monthly), involving various tests and medications in use, medications used in the past by the patient and individual response to each medication, allergies and intolerances, among other factors, which increases the risk of human error in the analysis and / or prescription of appropriate medications, or even in the doses that should be optimized individually for each patient. This situation substantially increases the risks and consequences for the patient and / or for the nephrologist or the clinic where he / she works.

[0022] Document Completion - After the physician's complex analysis, specific reports still need to be completed to enable the request for medications from the SUS Pharmacy, as well as the prescription, consent form (when the patient is using the medication for the first time), and to analyze which copies of exams need to be separated to send to the SUS pharmacy according to regulations. All these processes consume the physician's working time and are subject to human error. If the medication request process to the SUS pharmacy is incomplete or does not comply with regulations, it is subject to rejection, and the patient will not receive the appropriate medication, worsening their clinical indicators. This situation also increases the risks and consequences for the patient and / or the nephrologist or the clinic where they work.

[0023] Filling out the medical prescription - After the complex analysis by the doctor, he must still define the course of action and the reports for requesting medication and prescriptions, completing the medical prescription in the patient's medical record at the clinic so that the medication can be administered during hemodialysis, when applicable. This process is also subject to human error and consumes working time, increasing the risks and consequences for the patient and / or for the nephrologist or the clinic where he works. Petition 870250005827, dated 01 / 24 / 2025, page 10 / 36 7 / 27

[0024] Consumption of physician working hours - The situations mentioned above (manual interpretation of tests and medications, completion of documents and medical prescriptions) consume many hours of physician working hours throughout the month, recurring every month, reducing the physician's time available for clinical patient care. Furthermore, because it is a complex, recurring, and fundamentally important process, it makes the physician's work stressful, especially in dialysis units with a large volume of patients, which has led many nephrologists to seek other work alternatives or demand remuneration commensurate with the workload and stress.

[0025] Delay in using the ideal medication dose by the patient. Normally, hemodialysis clinics collect the monthly routine tests (mandatory by regulation) at the beginning of the month. It takes a few days for the results of these tests to be available to the doctors so that the analysis and adjustment of prescriptions can be made. Thus, the faster this process is completed, the sooner patients will start using the new optimized doses of medication, improving their clinical conditions. However, in many dialysis clinics, this process of analysis and completion of documents is only completed at the end of the current month, so that when the patient starts using the new optimized doses of medication, the next month has already arrived and the new collection of tests, which will not reflect an adequate time of use of the new medication dose, generating more erroneous analyses in the following month.In this way, a vicious cycle is perpetuated that, in addition to not generating benefits for the patient, leads to the excessive consumption of high-cost medications provided by the government. This difficulty, in turn, can trigger more regulatory measures to control medications, more oversight, and in some regions, a lack of medication availability.

[0026] Frequent changes in medications - As patients receive new test results every month, it is common for changes to be necessary. Petition 870250005827, dated 01 / 24 / 2025, page 11 / 36 8 / 27 Changes in medications in use and / or in their dosages often lead to low patient adherence to treatment, since patients, their families, and even the healthcare professionals at the clinic where treatment is being carried out may not be able to keep up with the frequent changes or understand the necessary adjustments, ignoring medication adjustments and consequently worsening the clinical outcome, compromising the safety of the treatment offered to the patient.Another problem related to this frequent change is the difficulty of making small adjustments to medications every month, since the doctor needs to perform several processes manually, often being forced to forgo such adjustments to balance work demands and respective emergencies. In some situations, the patient may continue receiving a non-optimized treatment for longer, until there is a "big" change that the doctor can handle, completing the complex chain of analyses and procedures and filling out all the associated bureaucracy.

[0027] Difficulty in controlling medication stock - Medications dispensed by the SUS pharmacy can be picked up by the patient or the dialysis clinic team in monthly batches. Once in possession of the medications, the dialysis unit is responsible for their proper storage, management, and administration. In this context, it is very important that the dialysis unit manages this accurately to ensure that each patient with approved medication release receives the dispensed dose(s). The larger the number of patients, the more difficult it is to perform this control, which, when done manually in static spreadsheets, increases the risk of errors in the process, as well as the risks and consequences for the patient and / or the nephrologist or the clinic where they work.

[0028] The present invention was conceived as a solution that solves all these problems simultaneously.

[0029] Prior to the present invention, the present inventor, as well as all Petition 870250005827, dated 01 / 24 / 2025, page 12 / 36 9 / 27 nephrologists to date, performed monthly analyses of their patients for the management of anemia and bone mineral density (BMD), as is standard practice. Realizing that this task was quite complex and consumed many hours of their medical team's work each month, they began creating objective clinical protocols to facilitate the application of the guidelines and regulations in force at the time. These protocols were applied manually by the team, but they already initiated the standardization of procedures among physicians. In 2010, the present inventor developed a tool called NOL – an acronym for Nephro Online, implemented by software that sought to provide solutions to some of the problems mentioned above. However, this tool had several limitations, which are resolved by the present invention.

[0030] Based on what can be inferred from the literature reviewed, no documents were found anticipating or suggesting the teachings of the present invention, so the solution proposed here has, in the inventor's view, novelty and inventive activity compared to the state of the art. Summary of the Invention

[0031] The present invention solves the problems of the prior art and provides a system and method to support the nephrologist, for improving data quality and optimizing the treatment of patients requiring dialysis, providing rapid and safe improvements in the control of anemia and BMD in CKD.

[0032] The present invention solves, among others, the following problems: updating the nephrologist; quick and accurate analysis of complex test results; providing suggestions for conduct to the nephrologist; standardization of conduct; minimization of errors; recording in the patient's medical record; generation of documents necessary to obtain medications from the SUS; control of medication stock.

[0033] It is therefore an object of the invention a system and method for improving data quality and optimizing the treatment of patients who need Petition 870250005827, dated 01 / 24 / 2025, page 13 / 36 10 / 27 dialysis sessions provide rapid and safe improvements in anemia and bone mineral density (BMD) control in chronic kidney disease (CKD).

[0034] The system and method of the invention comprises:

[0035] - a data collection interface;

[0036] - one or more algorithms for managing anemia in CKD;

[0037] - one or more algorithms for BMD management in CKD; and

[0038] - an interface to provide a dose suggestion for each medication for the patient.

[0039] In one embodiment, the system and method of the invention further comprises an interface selected from: document preparation and signing; monthly bulletin; reports, forms, or combinations thereof.

[0040] Given its nature, the invention can be implemented in different hardware / software sets. In one embodiment, the invention is implemented in PHP, HTML5 and Javascript languages, and the data is stored in a MySQL database. The “Analysis Controller” script processes the algorithms, which are the main innovation of the project.

[0041] In one embodiment, the data collection interface is done through integration with electronic medical records, laboratory data, or direct import of patients' clinical data, current and historical laboratory test results, and data related to the patient's medication use. All data is stored in a structured database for processing by algorithms.

[0042] In one implementation, the algorithms for managing anemia in CKD include anemia analysis by checking mandatory tests and regulatory periodicity, generating alerts in case of absence. The results are categorized as very low, low, normal, high, or very high. The system is configured to work with different algorithm parameters for each state / country that has different regulations. Next, the algorithm evaluates the recent change curve of each test, categorizing it as falling rapidly, falling slowly, stable, rising slowly, and rising rapidly. Then Petition 870250005827, dated 01 / 24 / 2025, page 14 / 36 11 / 27 analyzes clinical data: hemorrhage, inflammation, and transfusion. The analysis concludes with an evaluation of medication use data (epoetin alfa and iron hydroxide): current and previous use, 12-month history, and individual patient response. Finally, a suggested dose is developed for each medication; generally, the suggestions are categorized as "Do not use," "Start," "Maintain," "Increase," or "Decrease," respecting the particularities of each medication.

[0043] In one implementation, the algorithms for managing BMD in CKD include checking mandatory tests and regulatory periodicity, generating alerts in case of absence. The results of the mandatory tests are categorized as very low, low, normal, high, or very high. The system is designed to work with different algorithm parameters for each state / country that has different regulations. Next, the algorithm evaluates the recent change curve of each test, then evaluates clinical data: history of parathyroidectomy and amount of calcium and phosphorus in the diet, and finally analyzes medication use data, calcium carbonate, sevelamer, cinacalcet, paricalctiol, and calcitriol, where it analyzes current and previous use and the patient's individual response to the doses used.The analysis concludes with the development of a suggested dosage for each medication, which can be categorized as "Do not use," "Start," "Maintain," "Increase," or "Decrease," respecting the specific characteristics of each medication.

[0044] In one implementation, the document creation and signing interface includes the following settings: after confirming anemia and BMD diagnoses, the system creates the LME documents, prescriptions, consent forms, and monthly report as needed for each. It automatically manages LMEs, requesting initial, adjustment, and renewal requests as necessary. It digitally signs documents with the physician's A1 certificate if installed.

[0045] These and other objects of the invention will be immediately appreciated by those skilled in the art and will be described in detail below. Petition 870250005827, dated 01 / 24 / 2025, page 15 / 36 12 / 27 Detailed Description of the Invention

[0046] The present invention solves the problems of the prior art and provides a system and method to support the nephrologist in improving data quality and optimizing the treatment of patients requiring dialysis.

[0047] In one embodiment, the invention is implemented by software, called NAI, which solves the technical problems of the sector, providing quickly and safely the most up-to-date information on the control of anemia and BMD in CKD.

[0048] The system and method of the invention comprises the following elements:

[0049] - a data collection interface;

[0050] - one or more algorithms for managing anemia in CKD;

[0051] - one or more algorithms for BMD management in CKD; and

[0052] - an interface to provide a dose suggestion for each medication for the patient.

[0053] In one embodiment, the system and method of the invention further comprises an interface selected from: document preparation and signing; monthly bulletin; reports, forms, or combinations thereof.

[0054] Given its nature, the invention can be implemented in different hardware / software sets. In one embodiment, the invention is implemented in PHP 8.3.0, HTML5 and Javascript, and the data is stored in a MySQL 5.4 database. The normal workflow is for the user to authenticate with a login and password and access the work screen according to the authorization system. All access is performed through an index.php script that directs the flow according to the routes requested by the user through the links. In one embodiment, the “Analysis Controller” script is the “brain” of the invention, processing the algorithms that are the main innovation of the project and producing the suggested courses of action.

[0055] Data collection: the system receives data in various ways, whether Petition 870250005827, dated 01 / 24 / 2025, page 16 / 36 13 / 27 importing from other electronic health record systems (integration via API - Application Programming Interface), importing data spreadsheets, or even direct input of information into the program interface by the user. The types of data collected are clinical patient data, such as age, weight and height, vital signs, blood transfusions received, information on diet, hemorrhages, inflammations, surgeries, among others. Also, current and historical results of laboratory tests (numerical data) involved in the management of anemia and bone mineral density (BMD), for example, hemoglobin, ferritin, parathyroid hormone, calcium, phosphorus. And finally, data related to the patient's medication use, such as doses in use, dose history, allergies and intolerances. All data is stored in a structured database for later processing by algorithms.

[0056] Algorithms for managing anemia in CKD - ​​are developed based on the guidelines and legislation already mentioned, as well as the developer's clinical practice and experience. An analysis is the process where the algorithm receives the data, processes it, and generates a suggested course of action for each medication related to the management of anemia in CKD (epoetin alfa and iron hydroxide). Analyses are normally performed once a month when new routine monthly tests are collected, or whenever new relevant data is available. The physician has access to a screen to evaluate the data and the result of the analysis and decides whether to agree with the suggestion or make any manual changes, and finally confirms the course of action. Once the course of action is confirmed, the system does not perform further analyses on that data, waiting for the next month with new tests to perform the next analysis.

[0057] The anemia algorithm analysis process begins with checking the required tests and their frequency (hemoglobin must be monthly, ferritin and transferrin saturation index quarterly). If any of the required tests are missing, the system generates a "missing test" alert, which can be accessed on an alert review screen, and the user must arrange for the appropriate sample collection. Petition 870250005827, dated 01 / 24 / 2025, page 17 / 36 14 / 27

[0058] The results of mandatory tests are categorized as very low, low, normal, high, or very high (e.g., very low hemoglobin <7 g / dL, low <10 g / dL, normal 10 to 12 g / dL, high >12 g / dL, and very high >13 g / dL). These values ​​are those recommended by medical literature and regulations in 2025 and may be changed according to changes in medical knowledge or legislation. The system is designed to work with different algorithm parameters for each state / country that has different regulations.

[0059] After categorizing the current results, the algorithm evaluates the recent change curve of each test, compared to the last few months of available results, also categorizing them as falling rapidly, falling slowly, stable, rising slowly, and rising rapidly. Patients with more abrupt changes in results will have suggestions for medication adjustments even if the current test is not yet altered, but the projection of the test for the next month is altered considering the inertia of the recent change, for example a hemoglobin that was 11.5 last month and falls to 10.2 in the current month (still within the normal range), but as it fell 1.3 points in one month, the perspective is that it will fall another 1 point next month, reaching 9.2 which is outside the normal range, so the algorithm analyzes if the patient already uses alphaepoetin and will suggest an increase in the dose to avoid this possible drop.

[0060] Next, the algorithm evaluates non-mandatory tests (vitamin B12 and folic acid, which may be normal or low) and clinical data such as hemorrhage and inflammation, which are categorized as absent, mild, or severe, and lastly, whether a transfusion was received in the period since the last test result (absent or present).

[0061] The final part of the anemia algorithm refers to medication use data, specifically epoetin alpha and iron hydroxide, where it analyzes current use, previous use, doses used in the last 12 months, the patient's individual response to the doses used (for greater optimization in fine-tuning the dose recommendation), and the conversion of the absolute dose of epoetin alpha (in ampoules per month) to Petition 870250005827, dated 01 / 24 / 2025, page 18 / 36 15 / 27 international units / kg of patient weight / week to avoid doses exceeding the maximum recommended dose (subcutaneous dose maximum 300 IU / kg / week and intravenous dose maximum 450 IU / kg / week).

[0062] Once all these parameters have been analyzed and categorized, the algorithm can generate a dose suggestion for each medication. For alphaepoetin, the possibilities are "Do not use," "Start" (automatic calculation of 100 to 150 IU / kg / week), "Maintain current dose," "Increase dose" by 25 or 50% (respecting the maximum limit of IU / kg / week), or "Reduce dose" by 25 or 50%, and once the dose is defined, it rounds to the nearest multiple of 2,000 IU (smallest possible dose adjustment). For iron hydroxide, the possibilities are "Do not use," "Induction dose" with 8 ampoules per month, "Maintenance dose" with 4 ampoules / month, and "Minimum dose" with 2 ampoules / month.

[0063] Algorithms for managing BMD in CKD - ​​are developed based on the guidelines and legislation already cited, as well as the developer's clinical practice and experience. The same concept of "analysis" described in the anemia algorithm also applies here.

[0064] The BMD algorithm analysis process begins with checking the required tests and their frequency (calcium and phosphorus must be monthly, parathyroid hormone quarterly). If any of the required tests are missing, the system generates a "missing test" alert, which can be accessed on an alert review screen, and the user must arrange for the appropriate sample collection.

[0065] The results of mandatory tests are categorized as very low, low, normal, high, or very high (e.g., very low calcium <7 mg / dL, low < 8.4 mg / dL, normal 8.4 to 10.2 mg / dL, high >10.2 mg / dL, and very high >11 mg / dL). These values ​​are those recommended by medical literature and regulations in 2025 and may be changed according to changes in medical knowledge or legislation. The system is designed to work with different algorithm parameters for each state / country that has different regulations.

[0066] After categorizing the current results, the algorithm evaluates the curve Petition 870250005827, dated 01 / 24 / 2025, page 19 / 36 16 / 27 recent changes in each exam, compared to the last few months of available results, also categorized as falling rapidly, falling slowly, stable, rising slowly, and rising rapidly.

[0067] Next, the algorithm evaluates the clinical data: history of parathyroidectomy, which is categorized as absent, recent, or old, and the amount of calcium and phosphorus in the diet, which can be low, high, or very high.

[0068] The final part of the BMD algorithm refers to medication usage data, calcium carbonate, sevelamer, cinacalcet, paricalctiol and calcitriol, where it analyzes current use, previous use, doses used in the last 12 months and the patient's individual response to the doses used.

[0069] Once all these parameters have been analyzed and categorized, the algorithm can generate a dose suggestion for each medication. For calcium carbonate, the possibilities are “Do not use”, “Start replacement” (take away from meals), “Start chelating agent” (take with meals), “Maintain current dose”, “Increase dose” by 25 or 50% (respecting the maximum limit of 2g / day when chelating agent and 12g / day when replacing), or “Reduce dose” by 25 or 50%, and once the dose is defined, it rounds to the nearest multiple of 500mg (smallest possible dose adjustment). For sevelamer, the options are "Do not use", "Start chelating agent" (take with meals), "Maintain current dose", "Increase dose" by 25 or 50% (respecting the maximum limit of 9 tablets / day), or "Reduce dose" by 25 or 50%, and once the dose is defined, it rounds to the nearest multiple of 1 tablet / day (smallest possible dose adjustment).For cinacalcet, the options are "Do not use," "Start 1 tablet daily," "Maintain current dose," "Increase dose" by 25% or 50% (respecting the maximum limit of 9 tablets / day), or "Reduce dose" by 25% or 50%, and once the dose is defined, it rounds to the nearest multiple of 0.5 tablets / day (smallest possible dose adjustment). For paricalcitol, the options are "Do not use," "Start 1 ampoule / week," "Start 3 ampoules / week," "Maintain current dose," "Increase dose" by 25% or 50% (respecting the maximum limit of 6 ampoules / week), or... Petition 870250005827, dated 01 / 24 / 2025, p. 20 / 36 17 / 27 “Reduce the dose” by 25 or 50%, and once the dose is defined, it rounds to the nearest multiple of 0.5 ampoules / week (smallest possible dose adjustment). Finally, for paricalcitol, the options are “Do not use”, “Start 1 tablet / day”, “Start 3 tablets / day”, “Maintain current dose”, “Increase the dose” by 25 or 50% (respecting the maximum limit of 30 tablets / day), or “Reduce the dose” by 25 or 50%, and once the dose is defined, it rounds to the nearest multiple of 0.5 tablets / day (smallest possible dose adjustment).

[0070] Preparation and signing of documents: once the anemia and BMD algorithm procedures have been confirmed, the system can prepare the documents.

[0071] All the medications mentioned (except calcium carbonate) are provided by the SUS (Brazilian Public Health System) in accordance with the Clinical Protocol and Therapeutic Guidelines (PCDT), which establishes criteria for requesting them and requires the completion of a medical prescription and the Special Medication Report (LME) every 6 months or whenever it is necessary to change the dose of any of the medications, with the submission of a copy of specific tests. Furthermore, when starting a medication, the patient must sign a consent form, and for medications in the BMD protocol, a specific BMD report is also required.

[0072] All this management of which documents are needed at any given moment, and the completion of all these documents, is done automatically by the system, transparently to the user, who only needs to confirm the actions and request that the system print the documents. The system will analyze the new dose of each medication; if it is greater than zero, it compares it with the dose authorized in the current LME (Prescription of Medication Authorization): if there is no authorized dose = initial request; if the dose is greater than the authorized dose = adjustment request; if it is the LME renewal month = renewal request. After performing this analysis of each medication, the NAI (Nutrition and Information System) generates a unified LME with all medications and writes an automatic justification based on the information it has available. If the user has provided an A1 digital certificate for the installation of the Petition 870250005827, dated 01 / 24 / 2025, page 21 / 36 18 / 27 server, you will be able to have the PDF document digitally signed at the end of the process.

[0073] In one embodiment, the invention system produces the patient's Monthly Bulletin, a tool that presents the results of the last 7 months' tests in the form of a line graph highlighting in red those tests outside the normal range, as well as the prescribed doses of anemia and BMD medications for the last 7 months, integrated with the specific tests, so that the patient, family members, and healthcare team have a better understanding of the treatment, thus increasing adherence and clinical outcomes. We recommend that the Bulletin be printed monthly and distributed to the patient.

[0074] A relevant aspect of the present invention is the respect for the physician's autonomy, who always has the final decision, whether to accept the course of action suggested by the system because they consider it appropriate to the patient's current clinical situation, or to modify it according to their clinical experience and the patient's individuality.

[0075] The present invention was developed to provide a complete system capable of meeting the progressive increase in the number of patients served and the growth of the nephrology team in clinics or groups of clinics, and comprises extensive, complex and high-performance algorithms, with more precise and optimized solutions in a much faster and safer way. Some embodiments of the invention were tested in hemodialysis clinics in Londrina / PR (examples 1-4 below), showing results of high safety and efficiency for more than 1,000 patients and all nephrologists involved.

[0076] In one embodiment, the invention comprises a nephrologist's updating tool, using algorithms based on the most recent guidelines and current legislation. In this way, the suggested courses of action are always up-to-date, minimizing problems arising from the lack of updating of physicians. In addition, the recurring use of the system allows for the storage of a database that is always analyzed to identify lines of algorithms that are manually modified most frequently, in order to Petition 870250005827, dated 01 / 24 / 2025, page 22 / 36 19 / 27 understand the reasons for the modifications, in order to constantly improve the algorithms. This measure reduces the risk of errors and harm to patient treatment, minimizing conduct that does not comply with guidelines and current legislation, as well as reducing the risks of civil liability for the physician and the clinic where they work.

[0077] In one embodiment, the invention is a tool for rapidly and accurately analyzing complex examination data, providing the nephrologist with individualized and optimized treatment suggestions for each patient for the management of anemia and BMD in CKD. In one embodiment, said tool comprises algorithms and / or artificial intelligence refined / trained based on the clinical experience of nephrologists and the most current guidelines on the subjects and current Brazilian regulations.This implementation provides a comprehensive analysis that involves each patient's current tests, test history, medications in use and individual response history to each medication, clinical situation, allergies and intolerances of the patient, the tool providing a conclusion with a suggested course of action involving medications and doses individually optimized for the entire management of anemia and BMD, including all medications involved and non-pharmacological and nutritional approaches.

[0078] This implementation reduces human error and / or manual interpretation error. As the analysis performed by the system is extensive, involving the various tests and medications in use, medications used in the patient's past and individual response to each medication, allergies and intolerances, among other factors, the system's suggested course of action is accurate and minimizes the risk of human error in interpretation.This solution reduces the risk of errors, improves the quality of medical care, and reduces the risk of civil liability for doctors and clinics, in addition to reducing the number of working hours consumed by doctors.

[0079] Document completion - In one embodiment of the invention, the system completes the necessary documents for Petition 870250005827, dated 01 / 24 / 2025, page 23 / 36 20 / 27 implementation of procedures automatically and instantly, and allows printing or electronic sending of the digitally signed document with the responsible physician's A1 digital certificate. In this context, documents for a single patient or all patients of the clinic can be issued with just a few clicks, quickly and extremely efficiently. As the filling of document fields is based on information stored in a database, human error in this process is minimized.

[0080] Furthermore, the system understands what types of requests and documents are needed for each medication, and the context with the SUS pharmacy (initial, renewal or adjustment), since each context requires different and specific documents and exams, and the system provides all these documents transparently to the doctor, who only needs to worry about saying what dose of medication the patient needs, and the bureaucratic aspects of requesting this medication are automatically resolved by the system.

[0081] This solution minimizes the risk of medication denial due to bureaucratic problems or non-compliance with legislation, since the system's suggested procedures are always in accordance with legal guidelines, reducing the risk of civil liability for doctors and clinics. It also reduces the number of working hours and stress associated with doctors, as well as the need to recollect some tests to meet expiration date requirements when submitting a new request to the Health Department the following month.

[0082] Implementation of medical prescriptions in the patient's medical record at the clinic. Once the analysis, confirmation of procedures, and document production stages are completed, the NAI system can send a consolidated file to the patient's electronic medical record system at the clinic for recording information in the patient's medical record and effective administration of medications during hemodialysis. Automating this process reduces the risk of human error, the risk of civil liability for doctors and clinics, and reduces time spent. Petition 870250005827, dated 01 / 24 / 2025, page 24 / 36 21 / 27 worked by doctors.

[0083] Reducing physician working hours spent on data analysis - As previously mentioned, all stages of the process, when performed manually, consume a significant amount of physician working time each month. The solutions offered by NAI reduce the number of hours physicians spend on bureaucratic processes, allowing them to dedicate more time to direct patient care, improving the quality of care and reducing work-related stress. Clinics can optimize physicians' time, generating resource savings.

[0084] Creation of necessary documents - In one embodiment of the invention, the system provides, after the doctor confirms a course of action, the issuance of the documents necessary to request the medication from the competent authorities (for example, SPECIALIZED MEDICATION REQUEST REPORT - LME, consent forms, medical prescriptions, list of copies of necessary exams).

[0085] All these documents are automatically generated in a few seconds, according to the needs indicated by the legislation, already filled in with the necessary doses, patient data as registered in the database and digitally signed by the user physician's A1 Digital Certificate if they make it available for installation on the application server. The documents can be printed individually per patient or collectively (with filters by clinic, shift and dialysis room), optimizing the working time of the physician and team.

[0086] In one embodiment of the invention, the system provides for the issuance of a Monthly Information Bulletin, which consists of the automatic creation of an individualized information bulletin for each patient, summarizing their latest tests, medications to be used, and explanations in patient-friendly language about the main necessary procedures and guidelines. This bulletin is distributed monthly to patients, increasing the Petition 870250005827, dated 01 / 24 / 2025, page 25 / 36 22 / 27 understanding and involvement of patients and their families in the treatment.

[0087] In one embodiment of the invention, the system provides for recording in the patient's medical record, including the return of confirmed new procedures to the patient's clinic's medical record system, for effective recording in the medical record and prescription of doses to be administered in hemodialysis sessions. This return can be done automatically through integration between the NAI and the clinic's medical record system, or manually, with the physician entering the information into the medical record.

[0088] In one embodiment of the invention, the system provides an internal audit tool so that all actions confirmed by physicians, whether manually or by accepting the system's suggestion, can be audited by administrators, allowing them to assess whether there is consistency in the work of the medical team and continuous improvement in processes.

[0089] In one embodiment of the invention, the system provides a drug inventory control tool, through which the system automatically generates a spreadsheet to control the doses of medications requested from the SUS pharmacy and the current doses being used by patients. This facilitates internal drug inventory control and requests from the SUS pharmacy, bringing transparency to the periodic audits carried out by regulatory bodies.

[0090] In one embodiment of the invention, the system provides an Authentication and Authorization tool, through which individual access is protected by login and password, and optional two-factor authentication. Authorizations are based on user profile and permitted clinics, so that only users entitled to access sensitive information can do so.

[0091] In one embodiment of the invention, the system provides security and accessibility by running in a web environment with a TIER III or higher standard cloud server, with a secure connection and encryption in the transmission of data between server and client. Examples Petition 870250005827, dated 01 / 24 / 2025, page 26 / 36 23 / 27

[0092] The examples shown here are intended only to illustrate one of the numerous ways of carrying out the invention, however without limiting its scope. Example 1 - Standardization of Conduct through the use of the NAI System

[0093] In one embodiment, the invention comprises a tool for standardizing conduct.

[0094] Tests performed with the invention show that most of the actions suggested by the invention's system are followed by physicians, as they consider them to be aligned with current guidelines and legislation and to be correct for the specific clinical case in question. In this context, an internal study conducted within the NAI pilot project in three clinics in Londrina / PR (Table 1) demonstrated that most of the suggested actions were accepted by experienced nephrologists using the system, indicating that the quality of these suggestions is acceptable and can be considered reliable.

[0095] Table 1 - Use of the NAI System, suggestions provided and adjustments made Manual adjustment vs. NAI suggestion in 3 clinics Total analyses N 2067 % Algorithms on anemia Manual adjustment 398 19.3% NAI suggestion maintained 1656 80.1% Algorithms on BMD Manual adjustment 134 6.5% NAI suggestion maintained 1922 93.0%

[0096] The algorithm lines that are most frequently modified manually have been constantly updated and improved by the development team, leading to a progressive reduction in the need for manual adjustments and increased standardization. Petition 870250005827, dated 01 / 24 / 2025, page 27 / 36 24 / 27

[0097] In this way, the tool provides greater standardization in the management of anemia and bone mineral density (BMD), increasing patient safety. In addition, by increasing management efficiency, there is less expenditure on medications, staff, materials, and tests.

[0098] Example 2 - Reducing delays in using the ideal dose of medication and increasing productivity

[0099] A case study of the use of the invention's system to reduce the delay in the patient's use of the ideal medication dose was conducted in three clinics in Londrina / PR. The results showed that, on average, the time elapsed between the collection of samples and the effective modification of prescriptions after medical analysis was 12.8 days when performed manually. With the use of the NAI System of the invention, the time for adjusting the procedures was reduced by approximately 5 days, i.e., to an average of 7.6 days. Consequently, patients benefit from using the appropriate doses of medication for a longer period until the next sample collection. In addition, the more precise analysis of the new results with optimized doses provides a real productivity gain for the medical team of around 40.8%, as shown in Table 2.

[0100] Table 2 - Average number of days elapsed between sample collection and prescription adjustments in the medical record Comparison of 3 months Pre-NAI vs. 3 months with NAI in 3 clinics Control pre-NAI With NAI Variation P Clinic A 11.78 5.39 -54.3% <0.01 Clinic B 13.19 8.69 -34.1% <0.01 Clinic C 13.29 8.58 -35.4% <0.01 Total 12.8 7.6 -40.8% <0.01 Number of samples in 3 months Clinic A 581 661 Clinic B 62 125 Clinic C 346 395 Total 989 1181 Petition 870250005827, dated 01 / 24 / 2025, pages 28 / 36 25 / 27

[0101] Example 3 - Frequent changes in medications

[0102] Because the required analyses are quite precise and individualized, small dose adjustments must be generated every month to seek a fully optimized treatment. In this embodiment, the NAI System of the invention solves the problem of doctors having difficulty finding time to make small adjustments to medications, providing more appropriate treatment to the patient and more assertive organization of the stock to be made available by the SUS pharmacy.

[0103] A case study of the use of the NAI system in three clinics in Londrina / PR demonstrated that there was a significant increase in the number of prescription changes per patient / month, from 0.54 to 0.65 prescription changes / patient / month, representing an increase of 19.6% (Table 3).

[0104] Table 3 - Number of medication prescription adjustments / patient / month Comparison of 3 months Pre-NAI vs. 3 months with NAI in 3 clinics Control pre-NAI With NAI Variation P Clinic A 0.53 0.61 +14.0% <0.01 Clinic B 0.32 0.53 +66.4% <0.01 Clinic C 0.51 0.57 +12.0% <0.01 Total 0.50 0.58 +16.3% <0.01 Average number of patients in the 3 months Clinic A 374 381 Clinic B 68 83 Clinic C 231 261 Total 673 725

[0105] In one embodiment, the system additionally includes a Monthly Bulletin tool, which is distributed to patients monthly to increase understanding of their clinical condition and improve adherence of patients and families to treatment, as well as the entire multidisciplinary team (nursing, technicians, nutritionists, psychologists and social workers) who also become more involved in the treatment process. (Referred to) Petition 870250005827, dated 01 / 24 / 2025, pp. 29 / 36 26 / 27 The bulletin contains a clear summary of the necessary tests, medications, and procedures, allowing everyone involved in the process to better track even the frequent small changes in medications. In this embodiment, the invention's system is configured to allow access to the Clinical Bulletin via tablet, with simple filters that help to easily locate any patient during the care team's visits to the dialysis room.

[0106] Medication inventory control - Because the system automatically generates a dynamic spreadsheet with the doses requested from the SUS pharmacy for all medications for all its patients, as well as the doses currently in use, it can be used as an internal medication inventory management tool and increases the security of the entire process, also bringing greater transparency to regulatory bodies and reducing the risk of civil liability for the unit.

[0107] Example 4 - Clinical Results

[0108] In order to prove the efficacy and safety of NAI use, a comparative study of the clinical outcome of patients before and during NAI use was carried out. The results demonstrate that: (i) there was no significant worsening of any indicator; (ii) there was a significant improvement in the number of patients with hemoglobin, calcium and phosphorus within the recommended targets, as shown in Table 4 below.

[0109] Table 4 - Clinical indicators of Anemia and BMD. Comparison of 3 months pre-NAI vs. 3 months with NAI in 2 clinics Average test results Pre-NAI Control With NAI Variation P Hemoglobin (g / dL) 10.6 10.8 +1.8% 0.170 Calcium (mg / dL) 7.9 8.4 +6.3% <0.01 Phosphorus (mg / dL) 5.9 4.9 -16.9% <0.01 Percentage of patients within the clinical target range of the examination Pre-NAI Control With NAI Variation P Hemoglobin (> 10) 63.0% 70.4% +7.4% <0.01 Petition 870250005827, dated 01 / 24 / 2025, pp. 30 / 36 27 / 27 Calcium (8.4 - 10.2) 45.9% 57.4% +11.5% <0.01 Phosphorus (< 5.5) 50.7% 69.9% +19.2% <0.01 Number of samples in 3 months Hemoglobin 802 929 Calcium 787 927 Phosphorus 787 930

[0110] Those skilled in the art will appreciate the knowledge presented here and may reproduce the invention in the forms presented and in other variants and alternatives, covered by the scope of the following claims. Petition 870250005827, dated 01 / 24 / 2025, pp. 31 / 36

Claims

1 / 1 Claims 1. A system and method for improving the diagnosis, prognosis, and / or clinical management of anemia and / or bone mineral metabolism disorders in chronic kidney disease, characterized by comprising: - a data collection interface; - one or more algorithms for managing anemia in CKD; - one or more algorithms for managing BMD in CKD; and - an interface to provide a suggested dose for each medication for the patient.

2. System and method according to claim 1, characterized by additionally comprising an interface selected from: preparation and signing of documents; monthly bulletin; reports, forms, or combinations thereof. Petition 870250005827, dated 01 / 24 / 2025, pp. 32 / 36