endocrine and kidney diseases - somonini

Dialysis

• Dialysis is a physical therapy that replaces kidney function but doesn't cure the kidneys
• Dialysis has improved over the last 20 years but remains imperfect
• Good dialysis can replace a maximum of 10% of natural kidney function

Functions of Dialysis

• Dialysis removes waste materials and toxins like creatinine, urea, potassium, and phosphorus from the blood
• It removes excess water via ultrafiltration to maintain fluid balance
• Dialysis doesn't maintain bone health, improve bone turnover, maintain erythropoietin production, or promote renal repair

How Dialysis Helps

• Dialysis removes waste materials
• Dialysis removes fluids
• Dialysis maintains the body's chemical balance

Types of Dialysis

• Haemodialysis
• Peritoneal dialysis

Haemodialysis

• "Haemo" refers to blood
• Haemodialysis purifies blood from waste and excess fluids
• The process involves blood passing through a filter called a dialyzer in a dialysis machine
• The dialyzer purifies the blood, which is then returned to the body
• Haemodialysis is typically done in the hospital

Haemodialysis Procedure

• Blood is taken from the patient via a blood pump and sent through the dialyzer, then returned to the patient
• Dialysis requires vascular access (fistula, catheter, etc.), a machine with a blood pump and monitor, and a purifying liquid
• Blood purification occurs in the dialyzer, which has blood passing on one side and dialysate fluid on the other

Basic Principles of Dialysis

• Dialysis relies on diffusion, based on concentration, and convection, based on pressure
• Pressure difference across the filter removes fluids and waste
• Dialysis combines these principles but can rely on only one in specific cases

Physical Principles of Dialysis

• Blood purification occurs via a semipermeable membrane separating blood from dialysis liquid
• Diffusion allows transit of materials like electrolytes, creatinine, and urea through the membrane
• Toxic materials diffuse from high concentration in the blood to the dialytic fluid, aiding blood purification

Diffusion in Dialysis

• Membranes selectively eliminate non-essential elements
• Movement occurs from high to low concentration along an electrochemical gradient
• Smaller molecules move faster than larger ones
• Small waste elimination is directly proportional to dialysate flow
• Increasing dialysate and blood speed improves dialysis

Ultrafiltration in Dialysis

• Ultrafiltration involves applying a pressure difference to remove both fluids and waste materials, known as solvent drag
• Removing waste and fluids is important for patients with end-stage kidney disease who can't eliminate excess fluid

Haemodialysis: Critical Success Factors

• Good blood flow is necessary for successful dialysis
• Anticoagulants are administered to prevent blood coagulation in the extracorporeal circuit
• A patient needs to be able to hemodynamically tolerate dialysis
• Dialysis uses 100-200 liters of water per single patient per dialysis, patients usually go 3 times a week, meaning that we consume 300-600 liters of water per week.

Fistula and Graft

• Good blood flow is needed to perform a successful dialysis treatment
• Natural veins blood flow is sufficient for dialysis session because it is 300-350 ml/min
• Fistula is specifically made by surgically preparing a specific vein and connecting an artery to it to obtain a blood flow of 1L/min
• If there isn't a good connection between an artery and a vein, a graft can be used

Permacath

• If a patient has arteriopathy and a fistula cannot be created a catheter can be used
• Catheters are called tunneled catheters and will remain in place for the rest of the patients life because they attach directly into the dialysis machine

Anticoagulation in Dialysis

• A systemic anticoagulant, commonly heparin, is needed to prevent coagulation in the dialysis machine.
• Some patients cannot use systemic anticoagulants
• Heparin is effective as it has a lot of antagonists that can stop heparin

Haemodialysis: Success Factors

• The patient needs to be able to have an adequate blood pressure and hemodynamics to tolerate the dialysis
• Patients are instructed to only drink about half a liter of water a day, but in cases such as anuric patients, where the patient drinks or eats causes an accumulation of fluids of about 2-4L

Haemodialysis: Problems

• Improved technology but still imperfect
• Can only replace a maximum of 10% of kidney function
• Access failure often requires surgical intervention or a new catheter placement
• Risk of permanent canulators increases risk of sepsis, risk of infection, hepatitis

Peritoneal Dialysis

• The peritoneum is the filter
• Peritoneal dialyis is performed every night at home, where haemodialysis is done in the hospital
• The patient goes to the hospital once a month to check performance and control the blood and urine tests
• It performs the same as haemodialysis but this time by inserting our peritoneum

Peritoneal Dialysis: Procedure

• A catheter (Tenckhoff) will be placed permanently into the abdomen connected to a machine that will put a fluid in, which will stay there for hours and absorb excess water to purify
• The procedure should be done at night and in an aseptic way in order to limit risk of sepsis or peritonitis

Fluid Removal in Dialysis Types

• Hemodialysis uses pressure to force, whereas peritoneal dialysis uses glucose with a specific concentration to form hyperosmotic liquid that absorbs the fluids from the patient

Peritoneal Dialysis: Success Factors

• The patient has to be highly motivated
• Patient has to be well trained to connect and disconnect from the machine and preserving an aseptic situation every night
• This results in a lower efficacy compared to haemodialysis
• However, if the aseptic situation is neglected, patients can develop abdominal infections (peritonitis)

Peritoneal Dialysis: Aspects

• Slow and continuous dialysis is well tolerated by patients with disease
• The diet is well more tolerated due to the continuous loss of fluids, but should still follow the guidance of a dietician

Peritoneal Dialysis: Problems

• Contraindications are for patients that already underwent a multitude of surgical procedures in the abdomen
• Old people that live alone cannot perform this type of treatment

Dialysis for ESKD patients

• We usually chose young patients that are well motivated for this treatment
• Or old patients with heart disease or poor vascular access
• The dietary compliance, nutritional elements, and drugs result in a complete restoration of equality

Pharmacokinetics of dialysis

• Kidneys also remove drugs from our body so the pharmacokinetics turns completely different in case of an ESKD patient

Drug Dialyzability: Factors

• Depends of on the characteristics of the drug, such like mass weight and water solubility.
• The larger the drag that harder that it is to remove the drug through the dialysis and the higher water solubility that higher it is possible

Drug Dialyzability: Categories

• Dialyzable→50%-100% removed
• Moderately dialyzable→20%-50% removed
• Slightly dialyzable→5%-20% removed
• Not dialyzable→

Case Report 1: Initial Presentation

• A young Chinese woman with no prior medical history presented with weakness, poor appetite, and bilateral ankle swelling that had increased over two weeks.
• She reported a 12 kg weight gain in less than a month.
• Physical examination revealed severe leg edema with a positive fovea sign, but was otherwise normal with normal blood pressure.

Nephrotic Syndrome Considerations

• Nephrotic syndrome is indicated by edema, low blood proteinuria, and high urine proteinuria.
• Fluid overload can be assumed, but nephrotic syndrome cannot be confirmed without meeting proteinuria dosage.
• Peripheral edema can have other causes, including heart failure, pulmonary hypertension, thrombosis, varicose veins, or hepatic failure.
• Calcium channel blockers can cause edema as a side effect.

Excluding Other Conditions

• Heart failure exclusion: Normal blood pressure doesn't rule it out due to possible preserved ejection fraction; perform echocardiography.
• Deep vein thrombosis exclusion: Look for pain, red skin, inflammation, and discomfort during physical examination.
• Nephrotic syndrome and hepatic failure exclusion: Perform blood and urine tests to check proteinuria, plasmatic protein levels, and hepatic function.
• Always ask about current medications.
• Different conditions can have the same clinical presentation.

Blood Test Results

• High proteinuria and cholesterol levels
• Normal creatinine
• Low calcium and plasmatic albumin

Proteinuria Assessment

• Physiological protein level is at 0.150 g/day
• Microproteinuria is defined as less than 0.5 g/day
• Macroproteinuria is between 0.150 g/day and 0.500 g/day
• Standard proteinuria is 3.5 g/day
• Nephrotic proteinuria above 3.5 g/day
• Non-nephrotic proteinuria between 0.5 g/day and 3.5 g/day
• Quantitative investigation
• Qualitative investigation with electrophoresis to determine DNA, RNA and protein separation by size and charge

Qualitative Investigation - Types of Proteinuria

• Glomerular proteinuria: Loss of proteins larger than 17 KD.
• Tubular proteinuria: Loss of proteins less than 17 KD.
• Selective proteinuria: Loss of a specific protein type, like albumin in minimal change disease.

Types of Plasma Electrophoresis

• Plasma electrophoresis is also based on protein shape
• Increased acute phase proteins (alpha-2 and beta) indicate inflammation
• Increased gamma proteins indicate chronic inflammatory disease
• Low protein levels or increased acute phase protein indicate nephrotic syndrome
• Selective increase in one gamma protein indicates myeloma disease.

Proteinuria Evaluation Steps

• First, assess if the proteinuria is normal which is more than 3.5g/day
• If a patient performed physical exams before the test, repeat the proteinuria test to verify persistence and exclude orthostatic proteinuria
• Orthostatic proteinuria evaluation steps:
• Observe high protein levels captured during the day
• Observe no protein levels captured during the night
• In that case it is benign and require regular checks
• If not orthostatic, quantify protein levels:
• Kidney disease is evaluated with biopsy if exceeding 3g/day
• Check quality of proteins if less than 3g/day
• If mostly losing albumin then evaluate for biopsy
• If tubular proteinuria then evaluate other diseases

Conditions Associated with Proteinuria

• Transient proteinuria (fever, excessive exercise, albumin infusion): Expect approximately less than 1 g/day of proteins in the urine.
• Orthostatic proteinuria (young patients): Proteinuria can be more than 2 g/day.
• Overflow proteinuria: Associated with myeloma.
• Glomerular proteinuria: Loss of proteins through the glomerulus.
• Tubular gestational proteinuria: Must be excluded as a possible cause.

Clinical Case Review: Nephrotic Syndrome

• Nephrotic proteinuria is likely with >3.5 grams proteinuria in 24 hours
• Normal creatinine levels
• Low Calcium levels
• High cholesterol (319 mg)
• High Lipids (>400mg/dL ) severe dyslipidemia)
• Low levels of albumin.

The Questions to Ask In this Situation

• What is the reasons for hyperlipidemia
• What are the reasons for the low level of protein
• What are the reasons for the low levels of calcium

Hyperlipidemia in Nephrotic Syndrome

• The liver attempts to increase albumin levels without selectively affecting lipids -> hyperlipidemia
• Proteinuria causes albumin loss, so the liver increases cholesterol production to compensate

Hypoalbuminemia in Nephrotic Syndrome

• Lost proteins through the urine
• Calcium binds to albumin -> low albumin leads to low calcium

Confirming a Nephrotic Syndrome Diagnosis

• Requires edema, proteinuria (over 3.5 g/day), and low albumin.
• High cholesterol, high lipids, and lipids in urine (hypercholesterolemia and lipiduria) may also be present.
• Missing one feature indicates nephrotic range proteinuria.
• Coagulation system alterations can occur due to losing regulatory elements in urine.

Nephrotic Syndrome: Age Considerations

• Children/Young Adults: Minimal change disease is most common (78%); kidney biopsy is often skipped. Focal segmental glomerulosclerosis is possible but less common and has a bad outcome.
• Adults: Possible conditions are membranous glomerulonephritis, focal segmental glomerulosclerosis, or other conditions.
• Kidney biopsy is essential to establish the diagnosis

Additional Considerations

• It is important to exclude all pathologies via blood test as adults
• Preeclampsia in pregnant women

Additional Information

• Nephrotic syndrome diagnosis is made by kidney biopsy
• Minimal change diseases are identified by loss of tight junctions in the podocytes

Podocyte Dysfunction

• Prevents protein retention in blood
• Protein loss happens via slit diaphragm
• Loss of foot processes also means anionic charge is not preserved

Albumin and Urine

• Urine contains 90% albumin of total protein amount in minimal change disease
• There is reduced albumin in the blood

Clinical Signs of Nephrotic Syndrome

• Anasarca
• Edema in legs, ankles, face, eyelids, and scrotum
• Pleural/pericardial effusion

High Lipid Level Mechanisms:

• Hepatic synthesis of lipids occurs to try and compensate loss of albumin
• Changes to urine production and metabolic regulations of lipogenesis leads to increased lipid and cholesterol production

Elevated Cholesterol and Lipids:

• Causes deposition of cholesterol, lipids, and fats near the eyes
• Condition is known as Xanthelasmas and signifies severe dyslipidemia

Infections and Complications of Nephrotic Syndrome

• Anasarca: Edema in ankles and abdomen
• Increased infection risk
• Large fluids collection
• Dilution of humoral factors
• Loss of IgG and complement factors
• Zinc and Transferrin loss in urine
• Impaired neutrophil function

Coagulability Factors of Nephrotic Syndrome

• Loss of regulation factor in urine leads to thrombosis, more specifically renal veins, from not regulating coagulation factors,
• Loss of vitamin D binding
• Loss of metals leading to metabolic alkalosis and acute kidney injury,

Infection Susceptibility and Edema

• Severe edema can directly damage the skin
• Loss of factors - IgG, zinc, transferrin, vitamin D binding globulin can lead to infection susceptibility

Fluid Overload in Nephrotic Syndrome

• Gastrointestinal edema can cause malabsorption of drugs
• IV infusion is more effective than oral administration of diuretics for volume overload

Kidney Biopsy Findings

• Biopsy can identify minimal change disease via electron microscopy
• Minimal change disease has normal glomerulus.
• It will show unhealthy Potocytes

Minimal Change Disease (MCD)

• Can occur in children and adult
• Its more common in children, representing 70-90% of cases.
• In 1/3 of children with MCD have a history of atopy.
• MCD is commonly found in males in Asian and African American
• Familial predistosition

Minimal Change Disease: Pathogenesis

• Loss of albumin preservation leads to nephrotic syndrome development

Minimal Change Disease: Clinical Signs

• Edema
• Proteinuria
• Hypoalbuminemia
• Microhematuria and hypertension can occur particularly in adults
• Kidney Damage is common
• End stage renal disease and renal vein thrombosis is the most common form of complication

Focal Segmental Glomerulosclerosis (FSGS)

• MCD can develop into it with age
• FSGS is a resistant form of kidney disease with affected glomeruli
• Conditions have lot of common feature, but they are now trying to determine whether its progressive form of pathology or two different pathologies
• Natural development can lead to an end stage kidney disease

Classifying Treatment Response: MCD and FSGS

• Ultimate healing: Patient has one relapse
• Partial Responder/Relapses: 10-20% of patient have continuous relapses and require low doses of therapy
• No responding patient : Less common
• Complete remission in adults happens in 80.4% after 8 weeks of therapy
• Complete remission in children happens in 93% after 8 weeks of therapy

Steroid Therapy and Alternatives

• Steroids are the first line of treatment
• Second-line therapies when steroids are ineffective:
  • Ciclofosfamide: 2 mg/Kg/day for 8-12 weeks
  • Micofenolato mofetile: 1-2 g/Kg/day for 6-12 weeks
  • Ciclosporin A: 100-150 mg/m²/day
  • Tacrolimus: 2-4 mg x 2/die
• Third-line of therapy is rituximab 1000/2800 mg in 2-4 doses

Addressing Steroid Resistance

• In children or young adults, steroid resistance after eight weeks of therapy leads to immunosuppressor use and a the first choice is usually cyclophosphamide.
• If Cyclophosphamide is not effective, Rituximab is given.
• Steroid resistance is considered when nephrotic proteinuria occurs after 8 weeks of treatment
• Minimal change is shifting to GSFS if steroid resistant conditions is not resolving

Autoimmune Implications

• Biopsies only sample a small part of the kidney and cannot completely evaluate of the whole thing
• Assumptions must be made like the disease will shift to focal Segmental Glomerulonephritis

The Role of Steroids:

• steroids are known to shut down the immune system due to irregularities of the immunity.

Case 2: Presentation

• 28 y/o male patient presents with high levels of creatinine levels
• Patient has spina bifida and congenital club foot and there's no chronic pathologies, nor chronic use of medication
• In the last 5 years multiple urine infection and reported there is no difficulty in urination and has fatigue, weakness, abdominal pain

CKD vs AKI:

• Elevated Serum Creatinine: 3.7 is seen along with anemia, low counts of calcium
• Urinalysis appears to be normal
• With the finding there is severe elevating of creatinine, and the first physician calls for urgent nephological consult
• CKD is very very probable because condition as those usually requires lots of months
• Conducted an ultrasound for the status of the kidneys and is a very easy test to perform without repercussion
• Spina bifida - condition could lead to severe problem if not corrected at birth

Clinical Manifestations During First Visit:

• With first physical appearances there is nothing, little blood in the young patient
• Followed up with the patients and found that patient creatinine is 4.3
• 212 of uraemia and found patient in metabolic acidosis

Diagnosis Consideration:

• First action as doctor need it to determine is it a CKD and or AKI
  • Patient has higher levels of parameters, elevated levels of urea, low level of hemoglobin and increased PTH-
  • Also high levels of potassium
  • Therefore performed ultrasound and they found high levels of dilation
  • What they are looking to is urine tract obstruction in the bladder related with irritated bladder
  • What they did for the patient is removing all urinary catheter and catheter to remove the obstruction
  • With alteration in blood samples are: Acidosis and Sodium, correct low levels, anemia by support with iron

Procedure for 28y/o patient:

• Placed catheter for urinary retention
• Started IV hydration
• Reduced Creatinine and Urea after a few days
• Been able to remove patient in discharge with still Creatinine left
• One month back to hospital patient appear with creatinine lower, but in the last six months creatinine is normal

Diagnosis Conclusion:

• Not a CKD
• Post -renal AKI
• Neurogenic bladder in patient with Spina Bifida

Additional info

• AKI definition relies on the time of the condition
• Spina Bfida can prevents to eliminate urine from the bladder - probably is linked with with neurologic deficiency

Presentation for case 3

• 73 y/o female arrived after in an emergent room with complaintions of asthenia and nausea after about one month Is reporting some new ongoing dyspnea
• Appendectomy back at age 40 With high blood pressure and impaired glucose, taking Amlopidine 5 g the dosage of this type of medication can reach 10mg per day
• Took ibuprofen in a week for lumbago

Clinical Manisfestation:

• Pressure of oxygen is 82%
• heart rate of 120 and is tachycardic
• On lungs there are no vascular sounds only crackly in the lungs with fluid from top to button, there are some lungs are not completely easy
• She actually accumulates a lot fluids from lungs to peripheral tissue, as also blood pressure looks very bad
• She might has hyperadreations

Treatment method

• Correct Hyposthenia and perform blood exam, ultrasounds as a patient is not producing and performing a catheter
• Blood exam looks like patient has 300 of creatinine and 329 with urea, very high levels because history of kidney failure
• High levels of potassium are dangerous, as leads easily to cardiac arrest
• After has hyperkalemia, correct that as can be dangerous for heart for cardiac issue

Blood test reveals

• hypercalcemia is too high, along with high phosphate with metabolic acidosis with no bicarbonates
• White and red cell implies patient has uric infection due to high density and can use CRB for any infection because can rich very high
• Also can leads to cardio alterations
• If hyperkalemia can use pacemaker to restore cell, or use calcium to stabilize the cells with Gluconate
• Thankfully starts to take diuretic or Furoesimide
• In context CkD don't start with high dose as can be dangerous start with low dose

Drugs and Other Actions

• Correct metabolic ACIDOSIS > correct that as that influence hipercalcemia
• Hiperglycemia > can contribute the to hiperkalemia
• Redone antihipertherapy Doubling amlodipine and Doxasozin as alpha blocker to reduce hemoglobin levels
• Also it is important blood exam can determine all factors and can reveal all problem

Conclusions and Final Result from Case study

• Ultrasounds of kidney shows acute pulmunary indicates patient cause, which can causes cardiological or nephrological causes
• No hydronephrosis so can say that post renal cause is not the reason for the kidney
• With high BP means oxygen reduces, starts with 5 liters minutes
• Blood is restricted usually with the blood can lead to damage to the point a non-invasive